Preliminary experiments in our laboratory suggest that the cAMP content of adenocarcinomas of the human colon is significantly lower than that of the normal surrounding colonic mucosa. Numerous studies in the literature have implicated cAMP in the regulation of cell growth and differentiation and have noted reduced levels of this nucleotide in some neoplastic cells. Evaluation of cAMP metabolism in human neoplasia may, thus, be of both theoretical and practical importance. Accordingly, we propose to extend our preliminary observations by: (1) comparing the cAMP content of both carcinomas and adenomas of the human colon to those of the surrounding colonic mucosa; (2) evaluating potential mechanisms leading to reduced basal cAMP levels in the carcinomas by examining adenylate cyclase activity and cyclic phosphodiesterase; and (3) comparing the cAMP responsiveness of normal colon and tumors to prostaglandins and other hormonal stimuli in vitro for the purpose of identifying differences in the hormonal regulation of cellular metabolism and/or changes in the pattern of surface sites for hormones in the tumors. In these portions of human tissue specimens obtained at the time of therapeutic surgery will be employed. In addition, colonic cAMP metabolism will be assessed in rats exposed to the colon carcinogen, 1,2, dimethylhydrazine. These investigations will include (1) comparison of the cAMP levels of the experimentally induced tumors to those of surrounding mucosa; (2) sequential biweekly evaluation of cAMP content of colon mucosa after exposure of rats to carcinogen and (3) assessment of the effects of in vivo administration of dibutyryl cAMP and theophylline on tumor formation in rats concomitantly treated with carcinogen. The latter studies may permit evaluation of the functional significance of cAMP levels in the pathogenesis of colonic carcinoma.